Dec. 1, 2020: ACTIVating translational science to treat COVID-19
The COVID-19 pandemic has poignantly demonstrated the meaning and importance of the NCATS mission to “get more treatments to more patients more quickly.” At NCATS, we and our scientist and patient partners live this mantra every day, and the pandemic has magnified our sense of urgency and the drive to innovate. For the first time in my professional lifetime, the consequences of untreatable disease are viscerally appreciated by all simultaneously. As a translational community, we must not only act now to rapidly develop safe and effective COVID-19 treatments but also capture the scientific, operational and behavioral changes that are allowing that rapid development, induced by the pandemic. When COVID-19 is over, we must apply what we have shown ourselves is possible to the thousands of other diseases that need new treatments just as urgently. If such lasting change can be achieved, it will be a silver lining to the terrible consequences of the pandemic.
To get more COVID-19 treatments to more people more quickly, NCATS currently is conducting and supporting COVID-19 research across the translational science spectrum, from diagnostic testing and serology to drug development and community engagement to clinical trials. This includes innovation in the design, recruitment and conduct of clinical trials to efficiently produce robust, medically meaningful and clinically useful results. NCATS’ Clinical and Translational Science Award (CTSA) Program hubs and Trial Innovation Network are providing their scientific and operational innovation expertise, capacity and geographical reach to numerous COVID-19 trials. The wide diversity of medical and scientific expertise in the CTSA Program network is critical given that COVID-19 affects so many organ systems, including lungs, heart, kidneys, brain and blood vessels.
A particularly serious complication of COVID-19 is “cytokine storm,” an overreaction of the body’s immune system that can lead to acute respiratory distress syndrome, multiple organ failure and other life-threatening complications. NCATS is implementing a Phase 3 clinical trial to evaluate if temporarily suppressing that overactive immune response can reduce the severity of disease, shorten hospital stays and, most important, save lives. The trial is part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership that was started in April 2020 to develop a national research response to speed the development of the most promising COVID-19 treatments and vaccines.
The trial, called ACTIV-1 Immune Modulators, is testing three immune modulator drugs, two of which currently are U.S. Food and Drug Administration approved for other indications (infliximab [REMICADE/Johnson & Johnson] and abatacept [ORENCIA/Bristol Myers Squibb]), and one (Cenicriviroc [AbbVie]) that is in late-stage investigational development. The ACTIV-1 trial design is an innovative adaptive master protocol. “Adaptive” means that the trial is designed to continuously monitor the benefits of the various treatments being tested and to continue or stop one or more of the treatments depending on ongoing analyses of safety and effectiveness. “Master protocol” means that multiple drugs are evaluated simultaneously using a single protocol with multiple substudies, which speeds up drug testing and makes it more efficient.
The trial began in mid-October and plans to enroll approximately 2,000 hospitalized adults with moderate to severe COVID-19 in the United States and Latin America. The CTSA Program and its Trial Innovation Network are playing key roles at more than 30 U.S. study sites to ensure that participants reflect the demographics of the country and the pandemic, which has disproportionately affected minority and rural communities. We expect the trial will be complete within six months.
The Biomedical Advanced Research and Development Authority (BARDA) of the U.S. Department of Health and Human Services (HHS) Office of the Assistant Secretary for Preparedness and Response and Operation Warp Speed — a collaboration among multiple government agencies, co-led by HHS, that aims to accelerate the development, manufacturing and distribution of medical countermeasures for COVID-19 — are funding ACTIV-1.
If you or a family member is hospitalized with COVID-19, I urge you to inquire about this trial and others. The HHS Combat COVID web portal also offers information about participating in clinical trials — including ACTIV-1 and other trials coordinated by NCATS — as well as donating blood and plasma.
Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences